Chagas disease is one of the most important endemic problems in Central and South America, for which no definitive chemotherapeutic or immunological treatment is available. Trypanosoma cruzi (T. cruzi) is the agent of Chagas disease. Infection with a protozoan parasite T. cruzi, the causitive agent of Chagas disease, occurs in an estimated 18 million persons throughout Latin America and is a major cause of chronic heart disease. Immune responses after T. cruzi infection are particularly complex due to the biochemical diversity of multiple parasite strains and influence of host-genetic factors. The result is a wide diversity in clinical manifestations of Chagas disease and, in some cases, the disruption of immune regulation leading to immunosuppression and/or development of autoimmunity. This parasite has a complex life cycle involving an epimastigote stage in the insect vector and two main stages in the mammalian host. One stage is present in blood (trypomastigote) and a second stage is intracellular (amastigote).
The acute phase of T. cruzi infection is often asymptomatic. The infection may remain quiescent for decades. Some patients may, however, develop a progressive chronic form of the disease with cardiac and/or digestive tract alterations. After the acute phase with parasitemia, parasite growth is usually controlled by the host and patients or animals enter into a chronic phase where few parasites are present in the blood.
Immune responses to protozoan infection are complex, involving both humoral and cell-mediated responses to an array of parasite antigens. Infection often involves multiple life cycle stages of these parasites, which adds to the diversity of antigens potentially important for the development of protective immunity. To examine the molecular basis of the immune responses elicited during these infections, recent efforts have focused on evaluating responses to defined parasite B- and T-cell epitopes.
T. cruzi infections are often subtle and long-lasting, making diagnosis crucial and problematic. Detecting antibodies against parasite antigens is a most common and reliable method of determining clinical and subclinical infections. Presently, serological tests use whole or lysed T. cruzi and require positive results on two of three tests, including complement fixation, indirect immunofluorescence, passive agglutination, or ELISA to accurately detect T. cruzi infection. The expense as well as difficulty in performing such tests reliably prevent the screening of blood or sera in many endemic areas.
Blood bank screening is particularly important in South America, where 0.1-62% of samples may be infected and where the parasite is frequently transmitted by blood transfusion. It is also important and of increasing concern that the blood supply in certain U.S. cities is contaminated with T. cruzi parasites.
Therefore, there is a need in the art for a greater understanding of responses to specific parasite antigens. Although several antigens of T. cruzi have been identified and characterized biochemically, limited data are available on the evaluation of human immune responses to these molecules.